title: One novel Dravet syndrome causing mutation and one recurrent MAE causing mutation in SCN1A gene.
abstract: Mutations in SCN1A gene, encoding the voltage-gated sodium channel α1-subunit, are found to be associated with severe myoclonic epilepsy in infancy or Dravet syndrome (DS), but only rarely with the myoclonic astatic epilepsy (MAE, or Doose syndrome). We report on two patients with SCN1A mutations and severe epilepsy within the spectrum of generalized epilepsy with febrile seizures plus syndrome (GEFS+), the phenotypes being consistent with DS and MAE, respectively. Analysis of SCN1A revealed a heterozygous de novo frameshift mutation (c.4205_4208delGAAA) in the patient with DS, and a recurrent missense mutation (c.3521C>G) in that suffering from MAE. The missense mutation has been reported in patients with neurological diseases of various manifestations, which suggests that this variability is likely to result from the modifying effects of other genetic or environmental factors. DS phenotype has been mainly found associated with truncation mutations, while predominantly missense mutations and very few prematurely terminating substitutions have been reported in GEFS+ patients.
authors.affiliation: National Genetic Laboratory, Sofia Medical University, Sofia, Bulgaria. igli4eto@yahoo.com
authors.forename: Iglika
authors.initials: I
authors.lastname: Yordanova
authors.forename: Tihomir
authors.initials: T
authors.lastname: Todorov
authors.forename: Petia
authors.initials: P
authors.lastname: Dimova
authors.forename: Dimitrina
authors.initials: D
authors.lastname: Hristova
authors.forename: Radka
authors.initials: R
authors.lastname: Tincheva
authors.forename: Ivan
authors.initials: I
authors.lastname: Litvinenko
authors.forename: Olga
authors.initials: O
authors.lastname: Yotovska
authors.forename: Ivo
authors.initials: I
authors.lastname: Kremensky
authors.forename: Albena
authors.initials: A
authors.lastname: Todorova
mesh_terms: D017668:Age of Onset; D000927:Anticonvulsants / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004569:Electroencephalography; D004831:Epilepsies, Myoclonic / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007223:Infant; D008297:Male; D020125:Mutation, Missense; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D000927:Anticonvulsants; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels